Captopril plus losartan in early post-infarction. Neurohormonal effects: a pilot study.
BACKGROUND
Suppression of the formation of angiotensin II (A II) is thought to be a major contributor to the hemodynamic response to angiotensin-converting enzyme inhibition (ACE-inhibitor) therapy. However, during ACE-inhibitor treatment, A II plasma levels may also recover through tissue chymase. This study has attempted to verify the feasibility, safety and tolerability of a combined treatment using captopril (75 mg/day) and losartan (25 mg/day), and to ascertain its ability to reduce the formation and action of A II in the early post-infarction phase of reperfused anterior myocardial infarction (AMI).


METHODS
Forty-four patients hospitalized for suspected AMI within 4 hours of the onset of symptoms, who were suitable for thrombolysis (first episode), in Killip class I-II, reperfused, treated with 75 mg/day of captopril within 3 days of admission and with a blood pressure level of more than 120 mmHg, were randomized (single-blind) into two groups that were similar with regard to age, sex, blood pressure, CK peak, ejection fraction, end-systolic volume and risk factors. Group A (22 subjects: 6 women/16 men) received captopril (75 mg/day) and placebo, while group B (22 subjects: 5 women/17 men) was given captopril (75 mg/day) plus losartan, initially at 12.5 mg and then at 25 mg/day thereafter (BP > 110 mmHg). Norepinephrine (NE) and A II plasma levels were measured on the third and tenth day after admission.


RESULTS
Ten days after admission, group B (captopril plus losartan) showed a significant decrease in blood pressure (BP) on an intragroup level (p < 0.001) as well as in comparison with group A (p < 0.001), with values of 108 + 6.4 and 118 + 11 mmHg respectively. At the same time interval, NE and A II values did not show significant differences within or between groups. CONCLUSIONS. For the first time, our data suggest that a combined captopril-losartan treatment is feasible and that it has no particular side effects. In addition, it shows no significant increase of A II that would be produced by losartan alone.
Di Pasquale
P
P
Coronary Care Unit, Ingrassia Hospital Palermo.
Cannizzaro
S
S
Longo
A M
AM
Maringhini
G
G
Iachininoto
R
R
Paterna
S
S
D000368:Aged; D000804:Angiotensin II / Q000097:blood / Q000187:drug effects; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D002216:Captopril / Q000008:administration & dosage*; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D019808:Losartan / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood / Q000188:drug therapy*; D009638:Norepinephrine / Q000097:blood; D010865:Pilot Projects; D016037:Single-Blind Method; D013997:Time Factors
D000806:Angiotensin-Converting Enzyme Inhibitors; D000804:Angiotensin II; D002216:Captopril; D019808:Losartan; D009638:Norepinephrine